Llosteric sensitization of proapoptotic BAX

Nature Chemical Biology

Volumn 13, Issue 9, 2017, Pages 961-967

  Pritz, Jonathan R ^a   Wachter, Franziska ^a   Lee, Susan ^a   Luccarelli, James ^a   Wales, Thomas E ^b   Cohen, Daniel T ^a   Coote, Paul ^a   Heffron, Gregory J ^a   Engen, John R ^b   Massefski, Walter ^a,c   Walensky, Loren D ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b NORTHEASTERN UNIVERSITY   (United States)

^c DANA FARBER CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4-PHENOXYPHENOL; DIPHENYL ETHER DERIVATIVE; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BINDING;

APOPTOSIS; CHEMISTRY; DOSE RESPONSE; DRUG DELIVERY SYSTEM; HUMAN; MOLECULAR MODEL; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY;

APOPTOSIS; BCL-2-ASSOCIATED X PROTEIN; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DELIVERY SYSTEMS; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; PHENYL ETHERS; PROTEIN BINDING; PROTO-ONCOGENE PROTEINS C-BCL-2;

EID: 85027859363     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/nchembio.2433     Document Type: Article

References (60)

1. Suzuki, M., Youle, R.J. & Tjandra, N. Structure of Bax: coregulation of dimer formation and intracellular localization. Cell 103, 645-654 (2000).
2. Edlich, F. et al. Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol. Cell 145, 104-116 (2011).
3. Czabotar, P.E. et al. Bax crystal structures reveal how BH3 domains activate Bax and nucleate its oligomerization to induce apoptosis. Cell 152, 519-531 (2013).
4. Edwards, A.L. et al. Multimodal interaction with BCL-2 family proteins underlies the proapoptotic activity of PUMA BH3. Chem. Biol. 20, 888-902 (2013).
5. Gavathiotis, E., Reyna, D.E., Davis, M.L., Bird, G.H. & Walensky, L.D. BH3-triggered structural reorganization drives the activation of proapoptotic BAX. Mol. Cell 40, 481-492 (2010).
6. Gavathiotis, E. et al. BAX activation is initiated at a novel interaction site. Nature 455, 1076-1081 (2008).
7. Barclay, L.A. et al. Inhibition of pro-apoptotic BAX by a noncanonical interaction mechanism. Mol. Cell 57, 873-886 (2015).
8. Ma, J. et al. Structural mechanism of Bax inhibition by cytomegalovirus protein vMIA. Proc. Natl. Acad. Sci. USA 109, 20901-20906 (2012).
9. Petros, A.M. et al. Solution structure of the antiapoptotic protein bcl-2. Proc. Natl. Acad. Sci. USA 98, 3012-3017 (2001).
10. Walensky, L.D. & Gavathiotis, E. BAX unleashed: the biochemical transformation of an inactive cytosolic monomer into a toxic mitochondrial pore. Trends Biochem. Sci. 36, 642-652 (2011).
11. Souers, A.J. et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat. Med. 19, 202-208 (2013).
12. Sattler, M. et al. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science 275, 983-986 (1997).
13. Lessene, G. et al. Structure-guided design of a selective BCL-X(L) inhibitor. Nat. Chem. Biol. 9, 390-397 (2013).
14. Tao, Z.F. et al. Discovery of a potent and selective BCL-XL inhibitor with in vivo activity. ACS Med. Chem. Lett. 5, 1088-1093 (2014).
15. Tse, C. et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 68, 3421-3428 (2008).
16. Bruncko, M. et al. Structure-guided design of a series of MCL-1 inhibitors with high affinity and selectivity. J. Med. Chem. 58, 2180-2194 (2015).
17. Cohen, N.A. et al. A competitive stapled peptide screen identifies a selective small molecule that overcomes MCL-1-dependent leukemia cell survival. Chem. Biol. 19, 1175-1186 (2012).
18. Kotschy, A. et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature 538, 477-482 (2016).
19. Leverson, J.D. et al. Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax). Cell Death Dis. 6, e1590 (2015).
20. Pelz, N.F. et al. Discovery of 2-indole-acylsulfonamide myeloid cell leukemia 1 (Mcl-1) inhibitors using fragment-based methods. J. Med. Chem. 59, 2054-2066 (2016).
21. Stewart, M.L., Fire, E., Keating, A.E. & Walensky, L.D. The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer. Nat. Chem. Biol. 6, 595-601 (2010).
22. Huhn, A.J., Guerra, R.M., Harvey, E.P., Bird, G.H. & Walensky, L.D. Selective covalent targeting of anti-apoptotic BFL-1 by cysteine-reactive stapled peptide inhibitors. Cell. Chem. Biol. 23, 1123-1134 (2016).
23. Gavathiotis, E., Reyna, D.E., Bellairs, J.A., Leshchiner, E.S. & Walensky, L.D. Direct and selective small-molecule activation of proapoptotic BAX. Nat. Chem. Biol. 8, 639-645 (2012).
24. Brahmbhatt, H., Uehling, D., Al-Awar, R., Leber, B. & Andrews, D. Small molecules reveal an alternative mechanism of Bax activation. Biochem. J. 473, 1073-1083 (2016).
25. Xin, M. et al. Small-molecule Bax agonists for cancer therapy. Nat. Commun. 5, 4935 (2014).
26. Zhao, G. et al. Activation of the proapoptotic Bcl-2 protein Bax by a small molecule induces tumor cell apoptosis. Mol. Cell. Biol. 34, 1198-1207 (2014).
27. Wang, K., Gross, A., Waksman, G. & Korsmeyer, S.J. Mutagenesis of the BH3 domain of BAX identifies residues critical for dimerization and killing. Mol. Cell. Biol. 18, 6083-6089 (1998).
28. Scott, D.E., Coyne, A.G., Hudson, S.A. & Abell, C. Fragment-based approaches in drug discovery and chemical biology. Biochemistry 51, 4990-5003 (2012).
29. Mayer, M. & Meyer, B. Characterization of ligand binding by saturation transfer difference NMR spectroscopy. Angew. Chem. Int. Ed. Engl. 38, 1784-1788 (1999).
30. Stockman, B.J. & Dalvit, C. NMR screening techniques in drug discovery and drug design. Prog. Nucl. Magn. Reson. Spectrosc. 41, 187-231 (2002).
31. Tan, C. et al. Auto-activation of the apoptosis protein Bax increases mitochondrial membrane permeability and is inhibited by Bcl-2. J. Biol. Chem. 281, 14764-14775 (2006).
32. Wei, M.C. et al. tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev. 14, 2060-2071 (2000).
33. Pagliari, L.J. et al. The multidomain proapoptotic molecules Bax and Bak are directly activated by heat. Proc. Natl. Acad. Sci. USA 102, 17975-17980 (2005).
34. Sarosiek, K.A. et al. BID preferentially activates BAK while BIM preferentially activates BAX, affecting chemotherapy response. Mol. Cell 51, 751-765 (2013).
35. McGovern, S.L., Helfand, B.T., Feng, B. & Shoichet, B.K. A specific mechanism of nonspecific inhibition. J. Med. Chem. 46, 4265-4272 (2003).
36. Irwin, J.J. et al. An aggregation advisor for ligand discovery. J. Med. Chem. 58, 7076-7087 (2015).
37. Julien, O. et al. Unraveling the mechanism of cell death induced by chemical fibrils. Nat. Chem. Biol. 10, 969-976 (2014).
38. Arnoult, D. et al. Cytomegalovirus cell death suppressor vMIA blocks Bax- but not Bak-mediated apoptosis by binding and sequestering Bax at mitochondria. Proc. Natl. Acad. Sci. USA 101, 7988-7993 (2004).
39. Poncet, D. et al. An anti-apoptotic viral protein that recruits Bax to mitochondria. J. Biol. Chem. 279, 22605-22614 (2004).
40. Kozakov, D. et al. The FTMap family of web servers for determining and characterizing ligand-binding hot spots of proteins. Nat. Protoc. 10, 733-755 (2015).
41. Engen, J.R. Analysis of protein conformation and dynamics by hydrogen/deuterium exchange MS. Anal. Chem. 81, 7870-7875 (2009).
42. Laiken, S.L., Printz, M.P. & Craig, L.C. Tritium-hydrogen exchange studies of protein models. I. Gramicidin S-A. Biochemistry 8, 519-526 (1969).
43. Printz, M.P., Williams, H.P. & Craig, L.C. Evidence for the presence of hydrogen-bonded secondary structure in angiotensin II in aqueous solution. Proc. Natl. Acad. Sci. USA 69, 378-382 (1972).
44. Shi, X.E. et al. Hydrogen exchange-mass spectrometry measures stapled peptide conformational dynamics and predicts pharmacokinetic properties. Anal. Chem. 85, 11185-11188 (2013).
45. Hsu, Y.T. & Youle, R.J. Nonionic detergents induce dimerization among members of the Bcl-2 family. J. Biol. Chem. 272, 13829-13834 (1997).
46. Goping, I.S. et al. Regulated targeting of BAX to mitochondria. J. Cell Biol. 143, 207-215 (1998).
47. Follis, A.V. et al. PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis. Nat. Chem. Biol. 9, 163-168 (2013).
48. Lee, S. et al. Allosteric inhibition of antiapoptotic MCL-1. Nat. Struct. Mol. Biol. 23, 600-607 (2016).
49. Oltersdorf, T. et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 435, 677-681 (2005).
50. Leshchiner, E.S., Braun, C.R., Bird, G.H. & Walensky, L.D. Direct activation of full-length proapoptotic BAK. Proc. Natl. Acad. Sci. USA 110, E986-E995 (2013).
51. Bird, G.H., Crannell, W.C. & Walensky, L.D. Chemical synthesis of hydrocarbon-stapled peptides for protein interaction research and therapeutic targeting. Curr. Protoc. Chem. Biol. 3, 99-117 (2011).
52. Pitter, K., Bernal, F., Labelle, J. & Walensky, L.D. Dissection of the BCL-2 family signaling network with stabilized alpha-helices of BCL-2 domains. Methods Enzymol. 446, 387-408 (2008).
53. Hajduk, P.J., Olejniczak, E.T. & Fesik, S.W. One-dimensional relaxation- and diffusion-edited NMR methods for screening compounds that bind to macromolecules. J. Am. Chem. Soc. 119, 12257-12261 (1997).
54. Hwang, T.-L. & Shaka, A.J. Water suppression that works. Excitation sculpting using arbitrary waveforms and pulsed field gradients. J. Magn. Reson. A 112, 275-279 (1995).
55. Vranken, W.F. et al. The CCPN data model for NMR spectroscopy: development of a software pipeline. Proteins 59, 687-696 (2005).
56. Williamson, M.P. Using chemical shift perturbation to characterise ligand binding. Prog. Nucl. Magn. Reson. Spectrosc. 73, 1-16 (2013).
57. Grant, B.J., Rodrigues, A.P., ElSawy, K.M., McCammon, J.A. & Caves, L.S. Bio3d: an R package for the comparative analysis of protein structures. Bioinformatics 22, 2695-2696 (2006).
58. Skjßrven, L., Yao, X.Q., Scarabelli, G. & Grant, B.J. Integrating protein structural dynamics and evolutionary analysis with Bio3D. BMC Bioinformatics 15, 399 (2014).
59. Yao, X.Q., Skjßrven, L. & Grant, B.J. Rapid characterization of allosteric networks with ensemble normal mode analysis. J. Phys. Chem. B 120, 8276-8288 (2016).
60. Llambi, F. et al. A unified model of mammalian BCL-2 protein family interactions at the mitochondria. Mol. Cell 44, 517-531 (2011).